Motion in Acetylcholinesterase [acetyl]

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Classification Known Domain Motion, Hinge Mechanism [D-h-2]

Structures 1ACJ Complexed with tarcine [ PartsList ] 1ACK Complexed with edrophonium 1ACL Complexed with decamethonium [ PartsList ] 1AMN Complexed with trifluoroacetophenone [ PartsList ] 1FSS Complexed with fasiculin-II [ PartsList ] 1VOT Complexed with hyperzine A [ PartsList ]

Description Originally motion in this key neuro-protein was found through molecular dynamics simulation. These indicated the transient opening of a short channel, large enough to pass a water molecule, through a thin wall of the active site and suggested that substrate, products, or solvent could move through this "back door," in addition to the entrance revealed by the crystallographic structure. A comment by Joel Sussman on the radiation damage results: What is particularly fascinating in the study is that we see X-ray damage to a particular S-S bond in the protein acetylcholinesterase (AChE), while two other S-S bonds appear not to be affected. We see the equivalent S-S bond breaking, as well, in another species of AChE (drosophila ~30% sequence identity), and a very similar phenomena is seen in the protein lysozyme. It looks like we are seeing 'weak points' in protein structures that are particularly sensitive to ionizing radiation. As far as we know, this is the first experimental visualization of the breaking of a chemical bond in a protein structure by X-rays at cryogenic conditions.

Particular values describing motion Creation Date = 19971130 Experimental Methods = txm (Time-resolved, traditional X-ray and MD) Modification Date = 2000-01-29 20:51:57.000

References J L Sussman, M Harel, F Frolow, C Oefner, A Goldman, L Toker, I Silman (1992). Atomic Structure of Acetylcholinesterase from Torpedo californica: A Prototypic Acetylcholine-Binding Protein. Sci. 253: 874-879. [Medline info for 1678899] M K Gilson, T P Straatsma, JA A McCammon, D R Ripoll, C H Faerman, P H Axelsen, I Silman, J L Sussman (1994). Open "Back Door" in a Molecular Dynamics Simulation of Acetylcholinesterase. Sci. 263:1276-1278. [Medline info for 8122110] Weik M, Ravelli RB, Kryger G, McSweeney S, Raves ML, Harel M, Gros P, Silman I, Kroon J, Sussman JL (2000). Specific chemical and structural damage to proteins produced by synchrotron radiation. Proc Natl Acad Sci U S A Jan 18;97(2):623-628 [Medline info for 10639129]

Data and Graphics Figure showing radiation damage results PNAS cover

GO terms associated with structures Molecular function acetylcholinesterase activity, cholinesterase activity, catalytic activity Cellular component extracellular region Biological process acetylcholine catabolism in synaptic cleft, pathogenesis

Morphs

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Best representative Morph Morph name Structure #1 Structure #2 Residues [ ] [ ]

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Copyright 1995-2005 M. Gerstein, W. Krebs, S. Flores, N. Echols, and others
Email: Mark.Gerstein _at_ yale.edu